1-232415579-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_020808.5(SIPA1L2):c.4677C>T(p.Cys1559=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000666 in 1,613,916 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: SIPA1L2 NM_020808.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0940

Genes affected

SIPA1L2 (HGNC:23800): (signal induced proliferation associated 1 like 2) This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-232415579-G-A is Benign according to our data. Variant chr1-232415579-G-A is described in ClinVar as [Benign]. Clinvar id is 714105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.094 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1L2	NM_020808.5	c.4677C>T	p.Cys1559=	synonymous_variant	19/23	ENST00000674635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.4677C>T	p.Cys1559=	synonymous_variant	19/23		NM_020808.5	A1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152152 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000883 AC: 220 AN: 249142 Hom.: 0 AF XY: 0.000688 AC XY: 93 AN XY: 135178

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000358 AC: 524 AN: 1461646 Hom.: 2 Cov.: 30 AF XY: 0.000320 AC XY: 233 AN XY: 727118

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.00362 AC: 551 AN: 152270 Hom.: 4 Cov.: 32 AF XY: 0.00343 AC XY: 255 AN XY: 74452

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00218 Hom.: 1

Bravo AF: 0.00426

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	3.9
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143986958; hg19: chr1-232551325; COSMIC: COSV99477806;